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e16050 Background: The purpose is to evaluate the efficacy of sequential regimen using cetuximab-based doublet neoadjuvant chemotherapy, followed by surgery, if tumors resectable, and adjuvant cetuximab-based chemoradiotherapy in locally very advanced OSCC patients. Methods: Patients with T4a/b or N2b/c or N3 OSCC were enrolled to determine the response rate of cetuximab, cisplatin, and 5-FU neo-adjuvant chemotherapy. Cetuximab (400 mg/m2 loading, followed by 250 mg/m2 weekly x 6 weeks) was combined with 2 3-weekly cycles of cisplatin (100 mg/m2) and 5-FU (1000 mg/m2 x 3 days) as neo-adjuvant. Patients whose tumors became operable after neoadjuvant underwent radical surgery followed by adjuvant weekly cetuximab (250 mg/m2), cisplatin (30 mg/m2) and XRT (up to 70 Gy). Patients whose tumors remained inoperable after neoadjuvant received weekly cetuximab (250 mg/m2), cisplatin (30 mg/m2) and XRT (up to 70 Gy). Results: 33 patients were enrolled from Dec. 2009 to Jan. 2011. Average age was 47.3 years. 51.5% had primary lesion in buccal mucosa and 21.2% on tongue. 66.7% and 27.2% had T4b or T4a disease respectively, while 72.7% had N2b/N2c/N3 disease. 28/33 completed treatment course. On ITT analysis, 39.4% (13/33) had partial response and 48.5% (16/33) had stable disease after neoadjuvant. 42.4% (14/33) underwent radical surgery after neoadjuvant, while another 9% (3/33) underwent surgery after bio-chemoradiation. The 1 year disease free survival (resected group), progression free survival (ITT group), and overall survival (ITT group) were 48.8%, 73.2%, and 51.7% respectively. The most common grade 3/ 4 adverse event in neo-adjuvant phase was vomiting (16.1%), while mucositis (75%) and dermatitis (42.8%) accounted for major grade 3/ 4 adverse events during bio-chemoradiation. Conclusions: Cetuximab based sequential regimen was efficacious and well tolerated in improving treatment outcomes in locally very advanced OSCC patients with manageable side effects.

95 Background: We sought to clarify the influence of a positive or close superficial or deep mastectomy margin on the risk of LRR. Methods: We reviewed the charts of 561 consecutive women who underwent mastectomy without radiation for newly diagnosed in situ or invasive breast cancer between 1998 and 2005. The study cohort consists of 167 of these women who had a positive or close (≤2 mm) superficial or deep surgical margin. LRR as the site of first recurrence (+/− simultaneous distant disease) and distant metastasis (DM) rates were calculated using the Kaplan-Meier method. The median age was 50 years. Forty-five (27%) had ductal carcinoma in situ (DCIS) only. Of the 122 women with invasive disease, 79% had T1, 18% T2, and 3% T3 tumors, and 25% had positive axillary nodes (range, 1-4; 68% 1 positive node). Twenty-nine (24%) of those with invasive disease had lymphovascular invasion. The superficial margin was positive in 61 (37%) and close in 69 (41%). The deep margin was positive in 28 (17%) and close in 51 (31%). Results: The median follow-up was 6.3 years (range, 1-12.4). The 5-year LRR rate was 5% (95% CI 2-10%) and the DM rate was 3% (95% CI 1-8%). Twelve patients had a LRR; this included the chest wall in 9 and the axilla in 4. Five of the 12 had positive nodes. Four of 92 (4%) with close margins had a LRR vs. 8/75 (11%) with positive margins (log-rank p=0.15). Of the 45 with pure DCIS, 1 (2%) had a LRR. Of those with invasive disease, LRR occurred in 1/28 (4%) who had invasive disease at (positive) or near (close) the superficial margin, 3/38 (8%) with DCIS at or near the superficial margin, 0/12 with invasive disease at or near the deep margin, and 1/12 (8%) with DCIS at or near the deep margin. Both margins were positive or close in 32/122 patients with invasive disease; 6 of these (19%) had a LRR. Conclusions: The risk of LRR in patients with a positive or close surgical margin after mastectomy is generally low. The benefit of post-mastectomy radiation in this population with otherwise favorable features is likely to be small. While there may be a higher risk of LRR in patients with disease at or close to both margins (likely representing extent of disease), numbers in these categories are small and these results should be interpreted with caution.

Materials/Methods: We reviewed records of 83 consecutive patients (pts) diagnosed with MIBC from 1997-2005. Microinvasion was defined using the AJCC definition with no focus of invasion larger than 1 mm. The median age at diagnosis was 53 years. The cumulative incidence (CI) of local recurrence (LR) was estimated with nodal/distant recurrence as a competing event; the CI of nodal/distant recurrence was estimated with LR as a competing event. Time to recurrence was measured from the date of breast-cancer diagnosis. Pts were censored at the date of second malignancy (n = 1), contralateral breast cancer (n = 2), or date of last breast-cancer follow-up. Univariate predictors of LR were identified using the log-rank test and the effect estimates were determined using Cox proportional hazards regression.

10023 Background: Numerous preclinical studies demonstrate that anti-angiogenic agents increase the efficacy of radiation therapy (RT) against solid tumors. However, there have been no clinical studies of bevacizumab (BV) and RT (without chemotherapy) examining efficacy and biological effects. Methods: 20 pts with >5 cm, intermediate- or high-grade soft tissue sarcomas at increased risk of local recurrence (LR) received neoadjuvant BV and RT. Blood and tumor tissue were collected before treatment, after BV alone (for 2 wks), and after BV plus RT (for 6 wks). Serial perfusion CT scans assessed changes in tumor vasculature. Tumors were resected 6-7 wks following BV plus RT. Results: 13 extremity, 1 trunk, and 6 retroperitoneal tumors of varied histological subtypes were treated, and median tumor size was 8.25 cm. During treatment, there were no grade 4 toxicities, and 3 pts (15%) had grade 3 toxicities (hypertension, LFT elevation). Following surgery, 4 pts (20%) had major wound complications and one had a ...

6141 Background: Technologic advances in RT delivery have the potential to reduce errors via increased automation and built-in quality assurance (QA) safeguards. Intensity modulated radiation therapy (IMRT) is an increasingly utilized technology that delivers highly-conformal radiation by using multiple beams and beam angles. Although IMRT is more technically complex than traditional 2-dimensional (2D) and 3-dimensional (3D) RT techniques, it requires more QA safeguards and is highly automated, which may reduce the risk of human error. We hypothesized that IMRT is associated with a lower error rate in RT delivery than 2D and 3D RT delivery techniques. Methods: All errors in external beam RT delivery were prospectively recorded via a non-punitive error-reporting system at Brigham and Women's Hospital and the Dana Farber Cancer Institute. Errors are defined as any unplanned deviation from the intended RT treatment and are reviewed during a monthly departmental quality improvement meeting. We performed a ret...

Paramagnetic and superparamagnetic substances are used to trace stem cell in living organisms under magnetic resonance imaging (MRI). We compared paramagnetic and superparamagnetic substance for their labeling efficiency by using clinically widely used gadolinium chelates and iron oxide nanoparticles. Without the aid of transfection agent, human mesenchymal stem cells were labeled with each agent separately in different concentration and the optimized concentration was determined by maintaining same cell viability as unlabeled cells. Iron oxide nanoparticle labeling has a detecting threshold of 12 500 cells in vitro, while gadolinium chelates labeling could be detected for at least 50 000 cells. In life animal study, we found there is an eightfold sensitivity in cells labeled with iron oxide superparamagnetic nanoparticles; however, the magnetic susceptibility artifact would obscure the detail of adjacent anatomical structures. We conclude that labeling stem cells with superparamagnetic substance is more ...

We have developed a 46-inch TFT-LCD HDTV (high definition television — 1080p) with digital color management and image enhancement technologies. The panel uses premium MVA (multi-domain vertical alignment liquid crystals, and is fabricated on generation-5 glass substrates with ODF process (one drop filled liquid crystal process). It adopts the true wide format of 16:9. The viewing angle at a CR (contrast ratio) of 10:1 is greater than 170° in all directions. In the normal direction, CR is above 800. For conventional color management and image quality enhancement, we optimized the color performance between color-filters and backlight units as well as the properties of VA LC and polarizers. The outcomes include high color gamut (75% of NTSC) and brightness (> 600 nits). More advanced digital color management techniques include the application of vivid color mapping, and gamma correction by signal processing. For the quality of fast moving pictures, we have developed a new driving approach in conjunction with advanced VA LC's to achieve a response speed of 8 ms in average. The new approach compensates the slow transition between gray levels.

Purpose/Objective: Two randomized trials of patients treated by breast conserving therapy have demonstrated a significant increase in local control, for patients with negative margins, when a tumor bed boost was used in addition to whole breast irradiation. However, in patients with positive or close margins, the adequacy of tumor bed boost for local control and the optimal boost dose remain controversial. Published reports have suggested that tumor bed boost, even at higher doses, is not sufficient to overcome the negative effect of close or focally positive margins. The purpose of this study is to assess the impact of boost dose on local recurrence rate according to margin status. Materials/Methods: Six hundred thirty-five patients with clinical Stage I or II breast cancer were treated by breast-conserving surgery and radiation between 1992 and 1998 at the Massachusetts General Hospital. The median follow up was 54 months (range 6 ‐120). As an institutional policy, all pathologic specimens were re-reviewed upon referral and prior to de finitive treatment. Final margin status was determined based on the distance of invasive or in situ carcinoma from inked surgical margin: negative (no residual tumor or at least 2 mm from margin), close (less than 2 mm from margin), focally positive, or grossly positive. Patients received 50 Gy to the whole breast using 2 Gy per fraction, followed by a 10 Gy en face electron boost in 5 fractions for patients with negative margins and a 15‐18 Gy (15Gy/5 fractions in 28, 18 Gy/9 fractions in 80) high dose boost for focally-close, focally-positive or grossly-positive margins. Results: Sixty-five percent of the patients were T1, 35% T2, 72% N0, and 28% N1-2. Margin status was as follows: negative 71% (n450), close 18.4% (n117), and focally positive 11% (n68). There were no patients with grossly positive margin. The 5-year Kaplan-Meier local recurrence rates (LR) in the different margin groups were: 1.4% for negative margin, 3.2% for close margin, and 5.6% for focally close margin (p0.1169). When close (2mm) or focally positive margins were grouped together, the 5-year local failure rate was 4.1% (compared to LR of 1.4% in negative margin, p0.0115). Overall, the local recurrence rate was not statistically different in the standard versus high boost dose (p0.1745). Furthermore, in each of the margin groups, there was no statistically signi ficant difference between standard tumor bed boost and high tumor bed boost dose. The 8-year LR was identical to the 5-year LR. 5-year overall survival rates were 92.1% for negative margin, 89.9% for close margin and 79.4% for focally positive margin (p0.0087). Eight-year overall survival rates were 82.4%, 87.8%, and 64% (p0.0019), respectively. On univariate and multivariate analysis, only margin status was signi ficant in predicting local recurrence. Lymph node status, tumor size, age, and boost dose were not predictive of local recurrence (p0.12, p0.67, p0.98, and p0.34). Conclusions: This study shows increased local recurrence rate with close or focally positive final surgical margin in breast conserving therapy, which was not significantly altered by increasing the boost dose. Patients with negative surgical margin prior to radiation had low local recurrence rate of 1.4%, which was durable at 8 years. Patients with close or positive margin, however, had nearly 3x higher local recurrence rate, observed in the first 5 years of follow-up and persistent at 8 years. A risk of recurrence around 5% may still be regarded as acceptable in breast conserving therapy, but improving the margins surgically can further improve local control. Patients with close or focally positive margins should therefore undergo re-excision to render them margin-negative prior to radiation.

To investigate the feasibility of simultaneously assessing cerebral blood volume and diffusion heterogeneity using hybrid diffusion-kurtosis (DK) and intravoxel-incoherent-motion (IVIM) MR imaging. Fifteen healthy volunteers and 30 patients with histologically proven brain tumours (25 WHO grade II–IV gliomas and five metastases) were recruited. On a 3-T system, diffusion-weighted imaging was performed with six b-values ranging from 0 to 1,700 s/mm2. Nonlinear least-squares fitting was employed to extract diffusion coefficient (D), diffusion kurtosis coefficient (K, a measure of the degree of non-Gaussian and heterogeneous diffusion) and intravascular volume fraction (f, a measure proportional to cerebral blood volume). Repeated-measures multivariate analysis of variance and receiver operating characteristic analysis were performed to assess the ability of D/K/f in differentiating contrast-enhanced tumour from peritumoral oedema and normal-appearing white matter. Based on our imaging setting (baseline signal-to-noise ratio = 32–128), coefficient of variation was 14–20 % for K, ~6 % for D and 26–44 % for f. The indexes were able to differentiate contrast-enhanced tumour (Wilks’ λ = 0.026, p

Objectives This study sought to report the effect of carotid artery stenting (CS) on neurocognitive function (NCF) in patients with severe carotid artery occlusive disease, depending on baseline brain perfusion status. Background The effect of CS on NCF has been controversial. Methods We prospectively enrolled 61 patients with carotid artery disease (22 with occlusion, 39 with severe stenosis) in whom CS was attempted. Computed tomography perfusion and NCF assessments including Mini-Mental State Examination (MMSE), Alzheimer Disease Assessment Scale–Cognitive subscale (ADAS-Cog), verbal fluency, and Color Trails Test Parts 1 and 2 were applied before and 3 months after intervention. Results Successful recanalization was achieved in 14 of 22 occlusion patients (64%) and in all 39 severe stenosis patients. Two cases were excluded due to procedural cerebral complications. The patients were divided into 3 groups: group 1 (n = 8) consisted of patients with abnormal baseline ipsilateral cerebral perfusion in whom CS failed; group 2 (n = 33) consisted of patients with abnormal baseline ipsilateral cerebral perfusion in whom CS was successful; and group 3 (n = 19) consisted of patients without abnormal baseline ipsilateral cerebral perfusion in whom CS was successful. The demographics and baseline NCF were similar among groups. Only in group 2 was there significant improvement in ADAS-Cog (pre-procedure median [interquartile range]: 6 [4 to 9] vs. post-procedure: 5 [3 to 7], p = 0.002), MMSE (pre-procedure: 27 [25 to 28] vs. post-procedure: 28 [25 to 29], p = 0.004) and Color Trails Test Part 1 (pre-procedure: 100 [78.5 to 136.5] s vs. post-procedure: 97 [60 to 128.5] s, p = 0.003) after CS. Significant difference in changes from baseline was observed only in the Color Trails Test Part 1 among groups (group 1 vs. 2 vs. 3: 1.5 [−14 to 11.5] vs. −12.5 [−36.5 to 0.5] vs. −0.5 [−11 to 27], p = 0.0159). Significant correlation between the change of ipsilateral brain perfusion and MMSE (r = −0.33, p = 0.01) was also identified. Conclusions Successful CS for severe carotid stenosis/occlusion improves NCF, but only in patients with objective baseline abnormal cerebral perfusion.

Introduction Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids is a brainstem disorder characterized by perivascular pathologic reaction with lymphocyte infiltration and leading to diplopia, facial palsy, dysarthria, and gait ataxia. It was thought to be an autoimmune disorder without distinct pathogenesis. Chronic hepatitis B virus infection has been proposed in correlation with autoimmune diseases, including central nervous system demyelinating disease. Patients with chronic hepatitis B infection may develop the syndrome of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. Case presentation A 34-year-old Taiwanese man who had been a hepatitis B virus carrier for a decade presented to our emergency room. He had influenza symptoms and progressive symptoms of left hemifacial numbness, double vision, and an unsteady gait of 2 days’ duration. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids was diagnosed, with increased hepatitis B viral load at the same time. He had no past history of similar neurologic deficits, and his liver function tests had been within normal limits before this episode. After corticosteroid and entecavir treatments, his neurological deficits and neuroimaging anomalies improved and his serum hepatitis B virus DNA viral load normalized. Conclusions Hepatitis B virus infection may induce central nervous system autoimmune reactions, including chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. In such cases, concomitant administration of corticosteroids and antiviral agent was helpful. We suggest further investigations in patients with regulatory T cell dysfunction, which may assist in clarifying a loss of immune tolerance in patients with such disorders.